At NASA Headquarters, Washington, D.C. since 1974, he first served as a NASA program manager in charge of long-range planning of deep space manned activities (flights beyond Earth orbit) and he was an ardent advocate of manned space exploration and SETI.[3] While in NASA, he also worked with Gene Roddenberry as technical advisor to Paramount Pictures for Star Trek: The Motion Picture (1979), contributing, among other things, the hypothetical theory behind the faster-than-light space warp drive and the promotional slogan "Space — The Human Adventure Is Just Beginning".

From 1985 to 2000 he also lectured at the FH Aachen University at Aachen, Germany as an Honorary Professor. In 1995, von Puttkamer was awarded an honorary Doctorate in Philosophy by the Saarland University, Germany for his pioneering contributions to the understanding of space flight as a major cultural undertaking, challenge, and obligation of nations concerned about their future advancement and position in science, technology, industry, economy, education, and the humanities.

From 2009 until his death, Puttkamer provided management leadership at NASA Headquarters in Washington, D.C., on the programs of the International Space Station (ISS), for which he held special responsibilities as a Russia expert for the Russian segment and activities and daily on-orbit operation/increments, the Space Shuttle and, since 2004, President George W. Bush's Vision for Space Exploration, was stationed in the HQ Space Operations Mission Directorate (SOMD).

Jesco von Puttkamer died of a sudden flu-like illness on December 27, 2012.[3]

Von Puttkamer has said that among his most treasured achievements at NASA were his contributions to the Apollo program Lunar Landing in 1969, which fulfilled President John F. Kennedy's mandate of 1961; helping to rescue America's experimental space station Skylab after its near-disastrous launch into orbit on May 14, 1973, making it habitable and eminently successful for three sets of U.S. astronauts later that year; and also "rescuing" the backup Skylab version from being discarded so it could be publicly displayed in the National Air and Space Museum in Washington, D.C., instead of being sold for scrap.

He is the author of more than a dozen books on space flight, and, during his post-World War II student years in Germany and many well-known science fictionnovels. His novelette "The Sleeping God" was published in the English languageanthologyStar Trek: The New Voyages 2, edited by Sondra Marshak and Myrna Culbreath, ISBN 0-553-11392-5. His diary/book on the first lunar landing by Apollo 11 was published in 1982 in Beijing in a Chinese translation. A revised edition of this book was published for the 40th anniversary of the Apollo 11 mission in July 2009.[3]